Chalcone-based NF-?B inhibition for post-carcinogen lung cancer chemoprevention Chalcone-based compounds have demonstrated chemopreventive activities against various types of malignancies, including post-carcinogen lung tumorigenesis, potentially via inhibiting the activation of NF-?B pathway. Their chemopreventive efficacy, however, has never been optimized, which may potentially delay the translational development and reduce their potential impact to cancer prevention. We have recently optimized chalcone-based compounds to improve their NF-?B inhibitory activities, leading to a set of lead candidates with distinct NF-?B inhibitory profiles and one lead compound demonstrating potent anticancer activity in vivo against lung cancer xenograft, which is hypothesized to have significantly more potent chemopreventive activity against post-carcinogen lung tumorigenesis. The goal of this research is to identify a safe and more efficacious chalcone-based chemopreventive agent against post-carcinogen lung cancer development, which may eventually help former smoker to prevent lung cancer development, and to establish the importance of NF-?B inhibition in chemoprevention. Experimentally, we will synthesize six chalcone lead compounds, including the one that has demonstrated post-carcinogen lung cancer chemopreventive activity. These chalcones will be evaluated in A/J mice for their post-carcinogen chemopreventive efficacy. The chemopreventive efficacies among these candidates in combination with their pre-determined NF-?B inhibitory activities will establish the relationship between chemoprevention and NF-?B inhibition, which will indirectly determine the relative importance of NF-?B inhibition in chalcone-induced chemoprevention. The relevance of NF-?B inhibition to chemoprevention will be further explored by analyzing NF-?B biomarkers, such as I?Ba and p-P65, in the lung adenoma tissues.